In order to understand genetic basis underlying complex traits, such as morphology and energy metabolism, we are conducting genetic analyses based upon both of “Forward Genetics” using existing mouse mutants and “Reverse Genetics” using genetically engineered mice. In parallel, we are also compiling information of the genome diversity of inbred mouse strains, and developing new inter-subspecific consomic strains, in which every chromosome of a classical inbred strain C57BL/6J is replaced by the counterpart of a wild mouse-derived MSM/Ms strain. These bioresources are freely available for research community.
Enhancer adoption changes limb morphology:
(A) Hm has an insertion into the upstream region of Shh gene. Inserted fragment includes three interdigital enhancers. (B) X-ray micro-CT images of limb (P0). Shh is ectopically expressed in the interdigital region, and causes interdigital webbing in Hm . (C) We revealed the process that the morphological alteration in Hm was caused by the enhancer adoption.
Mouri, K., Sagai, T., Maeno, A., Amano, T., Toyoda, A., and Shiroishi, T. (2017). Enhancer adoption caused by genomic insertion elicits interdigital Shh expression and syndactyly in mouse. Proc Natl Acad Sci USA, doi: 10.1073/ pnas.1713339115.
Amano, T., Sagai, T., Seki, R., and Shiroishi, T. (2017). Two types of etiological mutation in the limb-specific enhancer of Shh. G3 (Bethesda) 7, 2991-2998.
Sagai, T., Amano, T., Maeno, A., Kimura, T., Nakamoto, M., Takehana, Y., Naruse, K., Okada, N., Kiyonari, H., and Shiroishi, T. (2017). Evolution of Shh endoderm enhancers during morphological transition from ventral lungs to dorsal gas bladder. Nat commun 8, 14300.